Frédéric Mal

Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C

Liver fibrosis is the main predictor of the progression of chronic hepatitis C, and its assessment by liver biopsy (LB) can help determine therapy. However, biopsy is an invasive procedure with several limitations. A new, noninvasive medical device based on transient elastography has been designed to measure liver stiffness. The aim of this study was to investigate the use of liver stiffness measurement (LSM) in the evaluation of liver fibrosis in patients with chronic hepatitis C. We prospectively enrolled 327 patients with chronic hepatitis C in a multicenter study. Patients underwent LB and LSM. METAVIR liver fibrosis stages were assessed on biopsy specimens by 2 pathologists. LSM was performed by transient elastography. Efficiency of LSM and optimal cutoff values for fibrosis stage assessment were determined by a receiver‐operating characteristics (ROC) curve analysis and cross‐validated by the jack‐knife method. LSM was well correlated with fibrosis stage (Kendall correlation coefficient: 0.55; P < .0001). The areas under ROC curves were 0.79 (95% CI, 0.73‐0.84) for F ≥ 2, 0.91 (0.87‐0.96) for F ≥ 3, and 0.97 (0.93‐1) for F = 4; for larger biopsies, these values were, respectively, 0.81, 0.95, and 0.99. Optimal stiffness cutoff values of 8.7 and 14.5 kPa showed F ≥ 2 and F = 4, respectively. In conclusion, noninvasive assessment of liver stiffness with transient elastography appears as a reliable tool to detect significant fibrosis or cirrhosis in patients with chronic hepatitis C. (HEPATOLOGY 2005;41:48–54.)

Worsening of hepatic dysfunction as a consequence of repeated hydroxyethylstarch infusions

BACKGROUND/AIMS Due to its apparent safety and low cost, hydroxyethylstarch (HES) is increasingly used as a volume expander. The aim of this retrospective study was to highlight the risk of hepatic dysfunction after iterative HES infusions. METHODS Between April 1996 and April 1998, nine patients were referred for worsening of their clinical condition after repeated HES infusions. Six patients had previous chronic liver disease, cirrhosis in four cases. All patients underwent a liver biopsy. RESULTS All post-HES liver biopsies showed diffuse microvacuolization of Kupffer cells, which was associated with focal hepatocyte vacuolization in seven cases. The vacuoles contained periodic acid Schiff positive material at their margins and were lysosomal by electron microscopy. The clinical symptoms of hepatic disease, although difficult to interpret in cirrhotic patients, worsened after HES infusions. Portal hypertension was noted in three non-cirrhotic patients. Serum alkaline phosphatase and gammaglutamyl transferase activities were increased when compared with previous values. Eight patients died, six of them within 1-4 weeks of hepatic failure or septic shock. In the only living patient, symptoms improved after HES withdrawal. CONCLUSIONS Repeated administration of HES could favour severe portal hypertension, liver failure and sepsis, particularly in the setting of chronic liver disease. The basis of these adverse effects is the lysosomal storage of HES in Kupffer cells and hepatocytes.

Impact on survival of surgery after concomitant chemoradiotherapy for locally advanced cancers of the esophagus.

BACKGROUND To evaluate the results of chemoradiotherapy with or without surgery in locally-advanced esophageal carcinomas (T3 and/or nodal involvement). METHODS One hundred twelve patients with locally-advanced carcinoma of the esophagus without histologically proven invasion of the tracheobronchial tree or distant visceral metastases were treated with concomitant chemoradiotherapy followed by re-evaluation; surgery was performed or chemoradiotherapy continued, based on tumor regression and the patients general status. Chemoradiotherapy consisted of concomitant 5-fluorouracil (5FU)(1 g/m(2) day 1-3), cisplatinum (50 mg/m(2) day 1 and 2), and external beam irradiation up to a dose of 40 or 43.2 Gy. After a 4-week rest period, radical esophagectomy or a new cycle of chemoradiotherapy (up to a total dose of 65 Gy) was performed. RESULTS A complete clinical response was obtained in 25.7% of the patients and a partial response in 45.9%. Fifty patients underwent surgery, but only 38 patients had an esophagectomy. Post-esophagectomy mortality was 5.3%. A complete histologic response rate of 23.7% was obtained. Two- and 5-year survival rates were, respectively, 41.5% and 28.6% for the whole population. According to multivariate analysis, prognostic factors for survival were Karnofsky index, esophagectomy, and response to chemoradiotherapy. Five-year survival for patients who experienced a partial response to radiation and chemotherapy was 49.1% for those who had surgery and 23.5% for those treated without surgery (p = 0.003). There was no obvious benefit for the small number of patients treated surgically after complete response to radiation and chemotherapy. Toxicity, essentially hematologic, was moderate. CONCLUSION For locally-advanced esophageal carcinomas, esophagectomy, after concomitant chemoradiotherapy, could improve the survival rate, especially for patients who responded partially to the latter.

Computed Tomography Versus Water-Soluble Contrast Swallow in the Detection of Intrathoracic Anastomotic Leak Complicating Esophagogastrectomy (Ivor Lewis): A Prospective Study in 97 Patients

Purpose:Water-soluble contrast swallow (CS) is usually performed before refeeding for anastomosis assessment after esophagectomy with intrathoracic anastomosis but the sensitivity of CS is low. Another diagnostic approach is based on analysis of computed tomography (CT) scan with oral contrast and of CT mediastinal air images. We undertook to compare them prospectively. Methods:Ninety-seven patients with an esophageal carcinoma operated by intrathoracic anastomosis were included prospectively in a study based on a CT scan at postoperative day 3 (without oral and intravenous contrast) and CT scan and CS at day 7. CT scan analysis consisted of assessing contrast and air leakage. In case of doubt, an endoscopy was done. Results:A diagnosis of anastomotic leak was made in 13 patients (13.4%), in 2 cases before day 7 and in 3 beyond day 7. At day 3, 94 CT scans were performed, but the diagnostic value was poor. In 95 patients with both CS and CT scan at day 7, CS disclosed a leak in 5 of 11, and CT scan was abnormal in 8 of 11. Leakage of contrast and/or presence of mediastinal gas had the best negative predictive value (95.8%). Endoscopy was done in 16 patients with only mediastinal gas at day 7 CT scan. It disclosed a normal anastomosis in 11, fibrin deposits in 4, and a leak in 1. Conclusions:In comparison with CS only, CT at day 7 improves the sensitivity and negative predictive value for diagnosing an anastomotic leak. In case of doubt endoscopy is advisable. This approach provides an accurate assessment of the anastomosis before refeeding.

Laparoscopic Heller's cardiomyotomy in achalasia. Is intraoperative endoscopy useful, and why?

AbstractBackground: Inappropriate length of the myotomy incision along the stomach, the most common technical fault during Heller’s cardiomyotomy, is related to the difficulty of identifying the gastro-esophageal junction, in particular during laparoscopic surgery. The goal of this study was to evaluate the contribution of endoscopy to gastro-esophageal junction identification during laparoscopic Heller’s cardiomyotomy. Methods: In a group of 19 patients with intraoperative endoscopy with laparoscopic Heller’s cardiomyotomy, surgical and endoscopic criteria for gastro-esophageal junction identification have been assessed. Then postoperative results of this group were compared with those of another group of 16 patients previously operated on without intraoperative endoscopy. Results: Endoscopic and laparoscopic criteria for gastro-esophageal junction identification were discordant in 11 patients (11/19, 58%). The cardia was in all these cases at a more distal site with endoscopic criteria. Complications ascribable to suboptimal technique were more frequent in the group without intraoperative endoscopy (7/16 patients) than in the other group (2/19 patients). Conclusions: Endoscopy during laparoscopic Heller’s cardiomyotomy is of great assistance in identifying the cardia, and thereby could improve surgical outcomes.

Ocular adnexal lymphoma and Helicobacter pylori gastric infection

There is a causal association between Helicobacter pylori (Hp) gastric infection and the development of gastric MALT lymphoma. In contrast, the link between Hp gastric infection and the development of extragastric lymphoma has not been thoroughly investigated. We, therefore, studied the prevalence of gastric Hp infection at initial diagnosis of ophthalmologic and nonophthalmologic extragastric lymphoma patients. Three cohorts of patients were studied: a first one of 83 patients with OAL, a second one of 101 patients with extraophthalmologic extragastric lymphoma, and a third one of 156 control individuals (control) without malignant lymphoma. Gastric Hp infection was investigated by histopathological analysis and Hp‐specific PCR assay on gastric biopsy tissue samples. We found gastric Hp infection in 37 OAL patients (45%), in 25 extraophthalmologic extragastric lymphoma cases (25%), and in 18 controls individuals (12%) (P < 0.0001 OAL/C and P < 0.01 OAL/extra‐OAL cases). Gastritis was found in 51% and 9% of Hp‐positive and Hp‐negative lymphoma patients, respectively (P < 10−4). Gastric Hp infection only correlated with MALT/LPL lymphoma (P = 0.03). There is a significant association between gastric Hp infection and MALT/LPL OAL. This suggests a novel mechanism of indirect infection‐associated lymphomagenesis whereby chronic local antigen stimulation would lead to the emergence of ectopic B‐cell lymphoma.

Pre-operative predictive factors of early recurrence after resection of adenocarcinoma of the esophagus and cardia.

OBJECTIVES To determine pre-operative predictive factors of early recurrence in patients with esophageal and cardial adenocarcinoma. PATIENTS AND METHODS We retrospectively analyzed consecutive patients who underwent resection for esophageal and cardial adenocarcinoma in our institution between October 1992 and October 2001. Patient files were studied and classified according to the occurrence of early recurrence (within one year) (group A) and patients without recurrence (group B). Pre-operative clinical, biological and radiological parameters were recorded. Both groups were compared in univariate and multivariate analysis. RESULTS One hundred patients underwent surgical resection. Tumor was located in lower esophagus in 71 cases and at the cardia in 29 cases. R0 resection was feasible in 95 cases. Hospital mortality was 2%. Survival rate at 3 years was 56%. Recurrence before 1 year occurred in 28 patients (group A) and not in 72 (group B). In univariate analysis, younger age (P=0.01), dysphagia (P=0.04) and percentage of weight loss (P<0.0004) were significantly different between both groups. Weight loss more than 10% was observed in 2 patients of group B, and in 9 patients of group A. In multivariate analysis, weight loss more than 10% was the only pre-operative factor associated with early recurrence (P=0.018). CONCLUSION Important weight loss could be a pre-operative predictive factor of early recurrence after resection of esophageal and cardial adenocarcinoma and surgery as first line treatment could be avoided in these patients.

Operative techniques to avoid near misses during laparoscopic hepatectomy

BACKGROUND The lack of a complete hepatic overview and tactile feedback during laparoscopic hepatectomy may result in near misses or fatal intraoperative complications despite the advantage of a magnified laparoscopic view. The aim of the study is to describe operative techniques and guiding principles with which to address near misses unique to laparoscopic hepatectomy and evaluate the intraoperative complication rate overtime. METHODS Data of 408 consecutive patients who underwent laparoscopic hepatectomy were reviewed. Representative operative techniques and guiding principles with which to address near misses and pitfalls unique to laparoscopic hepatectomy were evaluated among the patients by 2 surgeons. RESULTS Most near misses were due to lack of understanding of both the laparoscopic view and anatomic aspects unique to laparoscopic hepatectomy. Operative techniques and/or guiding principles with which to address these issues were demonstrated as follows: starting parenchymal transection at the declivitous parts; no ligation of the right or left portal vein before confirming the bifurcation; dissection of the short hepatic vein using a sealing device; dissection of the root of the hepatic vein using scissors; exposure of the middle hepatic vein, which is anatomically close to the hilar plate; and identification of V8 using intraoperative ultrasonography. The intraoperative massive bleeding due to vessel injury or surgical clip slippage occurred in 25 patients (6.1%), and its rate had a significant trend to decrease with increasing years. CONCLUSION We demonstrated operative techniques and guiding principles with which to address near misses in laparoscopic hepatectomy. The intraoperative massive bleeding rate trended to decrease over time.

CO.95 - Traitement par colle biologique des fistules post-opératoires en chirurgie colorectale

Resume La morbidite des fistules apres chirurgie colorectale est elevee et leur traitement est difficile. Leur obturation par injection de colle de fibrine a ete ponctuellement publiee. Ce travail presente les resultats d’une etude prospective chez 14 patients.

Traitement par colle biologique des fistules postopératoires en chirurgie colorectale

RésuméRésuméLa morbidité des fistules après chirurgie colorectale est élevée et leur traitement est difficile. Leur obturation par injection de colle de fibrine a été ponctuellement publiée. Ce travail présente les résultats d’une étude prospective chez 14 patients.Malades et méthodesDe juin 2004 à janvier 2008, les patients ayant une fistule postopératoire ont été inclus, à l’exclusion des fistules impliquant le vagin, celles de grand diamètre (> 1 cm) ou communiquant avec une cavité non drainée. Quatorze patients (10 H), d’âge moyen 63,5 ans, ont été traités; soit 11 cancers du rectum, 2 diverticulites et une tumeur stromale de la cloison recto-vaginale; trois sur 13 avaient reçu une radiothérapie préopératoire. Il s’agissait d’anastomoses colorectales (ACR), basses (n = 6) ou hautes (n = 4), dont neuf latéro-terminales, de trois anastomoses colo-anales (CA) et d’une suture rectale sans anastomose. Dix étaient des anastomoses mécaniques. Sept patients avaient d’emblée une stomie (CA + ACR basses). Le diagnostic de fistule était porté 11 fois sur l’imagerie (TDM, IRM), deux fois en endoscopie et une fois à l’examen clinique; neuf fois, il était porté précocement (< 14 jours) et cinq fois tardivement (> 57 jours). Six fois, une stomie secondaire a été nécessaire, toujours pour des fistules précoces. L’encollage a été effectué 1,5 fois en moyenne avec 1 à 3 ml de colle (Beriplast®); l’efficacité était jugée sur un scanner ou une IRM.RésultatsDouze fois sur l’imagerie, la fistule a été considérée comme obturée et la stomie a pu être retirée dans un délai moyen de 389 jours après sa mise en place, en moyenne 44 jours après le premier essai d’encollage pour les formes tardives et 168 pour les formes précoces. Dans deux cas, malgré une fermeture de la fistule, une infiltration présacrée persistait au scanner sans récidive tumorale. Le retard à la fermeture des stomies pouvait être lié à la nécessité d’une chimiothérapie postopératoire.ConclusionCette série, la plus grande rapportée d’encollage de fistules post-chirurgie colorectale coelioscopique, montre l’efficacité d’une prise en charge endoscopique. L’atout essentiel de cette technique est son absence de morbidité et une réelle efficacité, surtout en regard de l’alternative chirurgicale, notamment dans les fistules chroniques. Elle a permis une fermeture de la fistule dans 12 cas sur 14.AbstractAbstractFistula morbidity after colorectal surgery is high and such fistulae are hard to treat. There have occasionally been reports of closures using biological glue. This work presents the results of a prospective study concerning 14 patients.Patients and methodsBetween June 2004 and January 2008, all patients presenting with a postoperative fistula were included in the study, except if the fistula involved the vagina, was over 1 cm or communicated with a non-draining cavity. 14 patients (10 male) were treated, the average age being 63.5 years: 11 rectal cancers, 2 cases of diverticulitis and one stromal tumour of the recto-vaginal wall. Three out of 13 had had preoperative radiotherapy. The cases involved were 6 low and 4 high colorectal anastomoses (CRA), of which 9 were lateroterminal, 3 coloanal anastomoses (CA) and one rectal suture without anastomosis. Seven patients had spontaneous stoma (CA + low CRA). Diagnosis of the fistula was made by imaging in 11 cases (scan, MRI), twice by endoscopy and once by clinical exam; in nine cases, diagnosis was made early on (< 14 days) and in five cases it was late (> 57 days). In six cases, all diagnosed early, it was necessary to create a second stoma. Glueing was carried out one and a half times on average, using 1–3 mls of glue (Beriplast®); effectiveness was measured by CAT-scan or MRI.ResultsImaging showed the fistula to be closed in 12 cases and the stoma was removed an average of 389 days after it had been created, 44 days on average after the first glueing attempt for the later forms and 168 for the early forms. In two cases, despite closure of the fistula, presacral infiltration could be seen on the scan, without recurrence of the tumour. Late closures may have been connected with postoperative chemotherapy.ConclusionThis series, the most extensive report on gluing fistulas after colorectal laparoscopie surgery, shows that treatment by endoscopy is effective. The primary advantages of this technique are its absence of morbidity and real effectiveness, particularly considering the chronic fistula associated with the surgical alternative. Twelve of the 14 fistulae were successfully closed.